- NEW HETEROCYCLIC COMPOUNDS, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS, IN PARTICULAR AS ANTI-ALZHEIMER AGENTS
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The invention is related to compound which comprises at least one radical C=Y, Y being O or S, and an oxidable and non protonable nitrogen atom N wherein the distance (d) between the at least one carbon atom of the radical group C=Y and the nitrogen atom, when oxidized, is comprised between 0.3 and 0.8 nanometers. The invention is related to new heterocyclic compounds defined by formula G, their preparation, to pharmaceutical compositions comprising them and to their use as therapeutic agents, particularly in the treatment of neurodegenerative or Alzheimer disease.
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Page/Page column 115
(2008/06/13)
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- Hydroxy- and amino-substituted piperidinecarboxylic acids as γ-aminobutyric acid agonists and uptake inhibitors
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The syntheses of (3RS, 4RS)-4-hydroxypiperidine-3-carboxylic acid (4), (3RS, 5SRJ-5-hydroxypiperiden-3-carboxylic acid (20), (3RS, 4SR)-4-acetamidopiperidine-3-carboxylic acid (10), and (3RS, 5SR)-5-acetamidopiperidine-3-carboxylic acid (18), related to the specific γ-aminobutyric (GABA) uptake inhibitors (RS)-piperidine-3-carboxylic acid (nipecotic acid) and (3RS, 4SR)-4-hydroxypiperidine-3-carboxylic acid (21), are described. Furthermore, (3RS, 4SR)-3-hydroxypiperidine-4-carboxylic acid (14), related to the specific GABA agonist piperidine-4-carboxylic acid (isonipecotic acid), has been synthesized. The structures of 4, 10, 14, 18, and 20 have been established by 270-MHz 1H NMR spectroscopic analyses. The affinity of the compounds for the GABA receptors and for the neuronal (synaptosomal) GABA uptake system in vitro has been measured. Compound 14 interacts selectively with the GABA receptors but less effectively than isonipecotic acid and the cis-isomer 22. Compounds 4, 18, and 20 are inhibitors of the GABA uptake system, although much weaker than nipecotic acid and (3RS, 4SR)-4-hydroxypiperidine-3-carboxylic acid (21). Compound 10 is inactive in both test systems.
- Jacobsen,Labouta,Schaumburg,Falch,Krogsgaard-Larsen
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p. 1157 - 1162
(2007/10/02)
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